Periodic repression of Notch pathway genes governs the segmentation of Xenopus embryos
Periodic repression of Notch pathway genes governs the segmentation of Xenopus embryos
复制标题
DOI：
10.1101/gad.13.11.1486
复制
发表时间：
1999-06-01
影响因子：
10.5
通讯作者：
Kintner, C
中科院分区：
文献类型：
--
作者：
Jen, WC;Gawantka, V;Kintner, C
在脊椎动物胚胎的发育过程中，编码Notch信号通路组件的基因需要将旁轴中胚层细分为重复的节段结构，称为体节。当细胞形成潜在的体节时，这些基因被认为作用于分裂前期的中胚层，但它们的确切功能尚不清楚。为了解决这个问题，我们已经确定了两个新的基因，称为ESR-4和ESR-5，它们通过SU(H)依赖的Notch信号通路在非洲爪哇胚胎的体小体中转录激活。我们发现，这些基因的表达将每个体节分为前半部分和后半部分，并且这种表达模式是由一种机制产生的，当旁轴细胞进入关键区域并形成体节时，这种机制积极地抑制了Notch途径基因的表达。在体节形成过程中抑制Notch信号需要一个负反馈环，抑制该环中基因的活性对体节的大小有深远的影响。最后，我们提出了证据，一旦体粒形成，ESR-5就介导了一个正反馈回路，维持了Notch途径基因的表达。我们提出了一个模型，在该模型中，Notch信号在建立和维持非洲爪哇胚胎体节形成过程中的节段性特征方面发挥了关键作用。
During the development of the vertebrate embryo, genes encoding components of the Notch signaling pathway are required for subdividing the paraxial mesoderm into repeating segmental structures, called somites. These genes are thought to act in the presomitic mesoderm when cells form prospective somites, called somitomeres, but their exact function remains unknown. To address this issue, we have identified two novel genes, called ESR-4 and ESR-5, which are transcriptionally activated in the somitomeres of Xenopus embryos by the Su(H)-dependent Notch signaling pathway. We show that the expression of these genes divides each somitomere into an anterior and posterior half, and that this pattern of expression is generated by a mechanism that actively represses the expression of the Notch pathway genes when paraxial cells enter a critical region and form a somitomere. Repression of Notch signaling during somitomere formation requires a negative feedback loop and inhibiting the activity of genes in this loop has a profound effect on somitomere size. Finally we present evidence that once somitomeres form, ESR-5 mediates a positive feedback loop, which maintains the expression of Notch pathway genes. We propose a model in which Notch signaling plays a key role in both establishing and maintaining segmental identity during somitomere formation in Xenopus embryos.